Meta-analysis on vitamin D receptor and cancer risk

Serrano, Davide; Gnagnarella, Patrizia; Raimondi, Sara; Gandini, Sara

doi:10.1097/cej.0000000000000132

Cited by 39 publications

(14 citation statements)

References 110 publications

(65 reference statements)

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“…Gandini and colleagues reviewed 79 studies involving more than 52,000 different cancer cases and 62,000 controls to identify relevance of VDR BsmI, FokI, ApaI and TaqI polymorphism for various cancers and found BsmI, FokI and TaqI to be associated with CRC [ 27 ]. While we observed the ‘C’ allele of VDR-ApaI to confer 77% increased risk for CRC in patients > 57 years of age at the time of disease diagnosis, a recent meta-analysis by Serrano et al did not identify higher risk of CRC with VDR-ApaI but found a significant association with VDR-TaqI polymorphism [ 44 ]. Several other studies did not find an association of these VDR genetic variants with colorectal cancer risk in Caucasian populations [ 28 – 30 ].…”

Section: Discussioncontrasting

confidence: 61%

Association of Vitamin D Receptor Gene Polymorphisms with Colorectal Cancer in a Saudi Arabian Population

Al‐Khayal¹,

Awadalia²,

Vaali-Mohammed³

et al. 2016

PLoS ONE

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BackgroundVitamin D, causally implicated in bone diseases and human malignancies, exerts its effects through binding to the vitamin D receptor (VDR). VDR is a transcription factor modulating the expression of several genes in different pathways. Genetic variants in the VDR gene have been associated with several cancers in different population including colorectal cancer.ObjectiveTo assess the association of VDR gene polymorphisms in relation with colorectal cancer (CRC) in a Saudi population.MethodsThe polymorphisms of VDR gene (BsmI, FokI, ApaI and TaqI) were analyzed by the polymerase chain reaction amplification of segments of interest followed by Sanger sequencing. One hundred diagnosed CRC patients and 100 healthy control subjects that were age and gender matched were recruited.ResultsWe did not observe significant association of any of the four VDR polymorphisms with colorectal cancer risk in the overall analysis. Although not statistically significant, the AA genotype of BsmI conferred about two-fold protection against CRCs compared to the GG genotype. Stratification of the study subjects based on age and gender suggests statistically significant association of CRC with the ‘C’ allele of ApaI in patients >57 years of age at disease diagnosis and BsmI polymorphism in females. In addition, statistically significant differences were observed for the genotypic distributions of VDR-BsmI, ApaI and TaqI SNPs between Saudi Arabian population and several of the International HapMap project populations.ConclusionDespite the absence of correlation of the examined VDR polymorphisms with CRCs in the combined analysis, ApaI and BsmI loci are statistically significantly associated with CRC in elderly and female patients, respectively. These findings need further validation in larger cohorts prior to utilizing these SNPs as potential screening markers for colorectal cancers in Saudi population.

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Section: Discussioncontrasting

confidence: 61%

Association of Vitamin D Receptor Gene Polymorphisms with Colorectal Cancer in a Saudi Arabian Population

Al‐Khayal¹,

Awadalia²,

Vaali-Mohammed³

et al. 2016

PLoS ONE

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“…However, many of these studies presented significant associations [ 35 , 38 ]. Indeed, in a meta-analysis conducted by Serrano et al, [ 39 ] the authors presented a significant increased risk for CRC in the presence of tt and aa genotypes, with strong frequency variations present among different ethnic groups. Moreover, Gandini et al, [ 24 ] reviewed 79 studies with more than 52,000 cancer cases, including CRC patients, and 62,000 controls, and demonstrated that Bsm I, Fok I and Taq I polymorphisms are associated with CRC.…”

Section: Discussionmentioning

confidence: 99%

The Role of Vitamin D Receptor Gene Polymorphisms in Colorectal Cancer Risk

Messaritakis

Koulouridi

Sfakianaki

et al. 2020

Cancers

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Vitamin D deficiency has been associated with increased colorectal cancer (CRC) incidence risk and mortality. Vitamin D mediates its action through the binding of the vitamin D receptor (VDR), and polymorphisms of the VDR might explain these inverse associations. The aim of the study was the investigation of the relevance of rs731236; Thermus aquaticus I (TaqI), rs7975232; Acetobacter pasteurianus sub. pasteurianus I (ApaI), rs2228570; Flavobacterium okeanokoites I (FokI) and rs1544410, Bacillus stearothermophilus I (BsmI) polymorphisms of the VDR gene to colorectal carcinogenesis (CRC) and progression. Peripheral blood was obtained from 397 patients with early operable stage II/III (n = 202) and stage IV (n = 195) CRC. Moreover, samples from 100 healthy donors and 40 patients with adenomatous polyps were also included as control groups. Genotyping in the samples from patients and controls was performed using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP). A significant association was revealed between all four polymorphisms and cancer. Individuals with homozygous mutant (tt, aa, ff or bb) genotypes were more susceptible to the disease (p < 0.001). All of the mutant genotypes detected were also significantly associated with stage IV (p < 0.001), leading to significantly decreased survival (p < 0.001). Moreover, all four polymorphisms were significantly associated with KRAS (Kirsten ras oncogene) mutations and Toll-like receptor (TLR2, TLR4 and TLR9) genetic variants. In multivariate analysis, tt, aa and ff genotypes emerged as independent factors associated with decreased overall survival (OS) (p = 0.001, p < 0.001 and p = 0.001, respectively). The detection of higher frequencies of the VDR polymorphisms in CRC patients highlights the role of these polymorphisms in cancer development and progression.

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“…Obesity is well known to be implicated in the development and recurrence of breast cancer [10]; here we hypothesize that vitamin D action in adipose tissue may partially explain the role of vitamin D in cancers. The most common VDR polymorphisms reported to be associated with cancer and obesity are BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236), FokI (rs2228570) and Cdx2 (rs 11,568,820) [11, 12]. Likewise, previous epidemiologic studies indicate that obesity is associated with low levels of 25-hydroxy vitamin D3(25(OH) [13].…”

Section: Introductionmentioning

confidence: 99%

Vitamin D receptor gene polymorphisms affecting changes in visceral fat, waist circumference and lipid profile in breast cancer survivors supplemented with vitamin D3

et al. 2019

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Objective We investigated whether vitamin D receptor ( VDR ) polymorphisms are associated with circulating metabolic biomarkers and anthropometric measures changes in breast cancer survivors supplemented with vitamin D3. Methods One hundred sixty-eight breast cancer survivors admitted to Shohaday-e-Tajrish hospital received 4000 IU of daily vitamin D3 supplements for 12 weeks. Anthropometric measurements as well dietary, physical activity and plasma metabolic biomarkers assessments were performed before and after intervention. VDR polymorphisms were considered as the main exposures. Multivariate multiple linear regression analyses were used to determine the association between the VDR single-nucleotide polymorphisms (SNPs) and changes in metabolic and anthropometric measures in response to vitamin D3 supplementation. Results One hundred twenty-five (85%) women had insufficient and inadequate levels of plasma 25-hydroxy vitamin D (25(OH)D) at baseline. Compared to the AA genotype of the ApaI , the aa category showed greater increase in muscle mass [71.3(10.7131.9)] and higher decrease in LDL-C [− 17.9(− 33.6, − 2.3)] levels after adjustment for potential confounders. In addition, the heterozygous genotype (Bb) of the BsmI VDR was associated with higher increase in WC following vitamin D3 supplementation, compared to BB [2.7(0.1,5.3)]. Haplotype score analyses indicate a significant association between inferred haplotypes from BsmI , ApaI , TaqI and FokI , BsmI and Cdx2 VDR polymorphisms and on-study visceral fat changes. Conclusions Findings of this study showed that genetic variation in the VDR gene was associated with changes in cardio-metabolic parameters in breast cancer survivors, supplemented with vitamin D3, results could provide a novel insight into better understanding of which subset of individuals benefit most from normalization of vitamin D status. Trial registration This trial has been registered on the Iranian Registry of Clinical Trials (IRCT) under the identification code: IRCT2017091736244N1, registration date: 2017-11-10, http://www.irct.ir/trial/27153 and was approved by the ethics committees of the National Nutrition and Food Technology Research Institute (NNFTRI), Shahid Beheshti University of Medical Sciences (SBMU). Electronic supplementary material The online version of this article (10.1186/s12944-019-1100-x) contains supplementary material, which is available to authorized users.

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Meta-analysis on vitamin D receptor and cancer risk

Cited by 39 publications

References 110 publications

Association of Vitamin D Receptor Gene Polymorphisms with Colorectal Cancer in a Saudi Arabian Population

Association of Vitamin D Receptor Gene Polymorphisms with Colorectal Cancer in a Saudi Arabian Population

The Role of Vitamin D Receptor Gene Polymorphisms in Colorectal Cancer Risk

Vitamin D receptor gene polymorphisms affecting changes in visceral fat, waist circumference and lipid profile in breast cancer survivors supplemented with vitamin D3

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